Abstract: The synthesis of RNA is controlled through the interaction between RNA polymerase and DNA. During bacteriophage development both RNA polymerase and DNA are modified in ways which control the temporal sequence of gene expression. Studies of the role of the RNA polymerase modifications and changes in DNA structure promise to permit the test of the hypothesis that control of RNA synthesis in more complex systems can be explained by simple elaborations on these basic models. Two lines of inquiry are proposed. 1) Some of the experiments concern the mechanism of shutoff of E. coli transcription by the bacteriophage T4. The existence of an additional transcriptional factor has been postulated which may be required for the transcription of E. coli DNA in vivo but not in vitro. Inactivation of this factor after .T4 infection restricts transcription to the T4 template. Experiments are proposed to characterize and, eventually, to purify this factor. 2) Other experiments are designed to analyze the functions of RNA polymerase in T4 DNA replication. Some RNA polymerase mutants of the host are "cold sensitive" in their ability to replicate T4 DNA because the mutant RNA polymerase does not participate properly in some function directly required for T4 DNA replication. The existence of these mutants offers a unique opportunity to discover what may be an heretofore unknown function for RNA in DNA replication. Objectives: To use the molecular genetics approach to study the changes in the procaryotic transcription-replication machinery which occur during viral development.